- Email: [email protected]
MMP-13 (−77A > G) gene polymorphism is not a susceptibility factor of abdominal aortic aneurysm or aortoiliac occlusive disease
Abstracts
379
the endothelium but also of a variety of chemokines which have chemotactic and proinflammatory properties thereby contributing to vascular remodeling and thus to increased stiffness. The aim of this study was to determine whether the inflammation markers hsCRP, CCL22/MDC and its regulatory cytokines IL-4 and IFNγ are associated with increased AoS measured by PWV. hsCRP, CCL22, IL-4 and IFNγ were determined by immunoassays in 87 patients 63.3 ± 49.7 months after surgery for type A aortic dissection. We tested for correlations between these and haemodynamic parameters including 24-hour SBP, carotid-to-femoral PWV and progression velocity of aortic dilation (vØ). We found PWV and 24-hour SBP to be significantly correlated (r = 0.39; p b 0.001; ß = 0.345; p = 0.002) indicating a strong link between increased SBP and AoS. Among the inflammation markers, only CCL22 was correlated to PWV (r = 0.309; p = 0.056). Using the recommended cut-off value of 12 m/s for PWV, CCL22 was significantly higher in the high (15.3 ± 2.6 m/s) than in the low (9.9 ± 1.5 m/s) PWV group (603 ± 173 vs. 455 ± 210 pg/ml; p = 0.020). Regarding vØ, we found a significant correlation with 24-hour SBP (r = 0.336; p = 0.026; ß = 0.324; p = 0.046) but not with PWV and with hsCRP (r = 0.412; p = 0.005; ß = 0.337; p = 0.038) but not with CCL22. Taken together, these data indicate that in this population, 1° uncontrolled hypertension is related to increased aortic stiffness, 2° CCL22 appears to be a sensitive and specific marker of aortic remodeling, 3° aortic dilation (vØ) is related to increased SBP but not to stiffness and 4° aortic dilation appears to be independent of the CCL22 cascade.
aorta. The acquired samples were further processed, fixated and investigated. The wall of the experimental aneurysm was described by means of various parameters. All selected parameters specifically describe the aortic wall both in terms of its structure and function (elastin and collagen fibres, different types of smooth muscle cells, beta-catenin, vascularization, width of layers of aortic wall). Study results: By comparing the size of the aneurysms we did not find any statistically significant differences between both groups. However, in the first group there was an apparent trend in growing of the aneurysms that we did not find in the second group of pigs treated with statins. In all listed evaluated parameters the animals treated with statins showed statistically significantly better parameters, which can be considered as a histological picture of the vascular wall which is more stable and less damaged. Discussion: Better preservation of the elastin net and the contractile phenotype of the smooth muscle cells in treated group is in accordance with the recently described anti-inflammatory effect of statins in experimental aneurysms that had an unambiguously protective effect directly preventing progression of the aneurysm (Shiraya et al., 2009). A favorable effect of statins may be associated with (non-lipid) mechanisms which modify the function of the endothel, smooth muscle cells and population of monocytes– macrophages in the vascular wall (Koh, 2000). Based on the acquired information we assume that therapy with statins could be beneficial in prophylaxis of fast growth and ruptures of small aneurysms.
doi:10.1016/j.vph.2011.08.197
P.14.3 MMP-13 (−77A NG) gene polymorphism is not a susceptibility factor of abdominal aortic aneurysm or aortoiliac occlusive disease Aleksandra Korcza, Oliwia Zakerskaa, Katarzyna Pawlaczykb, Marta Molinska-Glurab, Grzegorz Oszkinisb, Ryszard Slomskia, Marcin Gabrielb a Polish Academy of Sciences, Institute of Human Genetics, Poznan, Poland b Poznan University of Medical Sciences, Poznan, Poland E-mail address: [email protected] (A. Korcz)
P.14.2 Progression of experimental abdominal aortic aneurysm is mitigated by statins Karel Houdeka, Jiří Moláčeka, Vladislav Třeškaa, Věra Křížkováb, Lada Eberlováb,c, Lukáš Nedorostb, Jiří Kobrd, Jan Baxae, Kirsti Witterf, Zbyněk Tonarb a Department of Vascular Surgery, Faculty of Medicine in Pilsen, Charles University in Prague, University Hospital in Pilsen, Czech Republic b Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University in Prague, Czech Republic c Department of Anatomy, Faculty of Medicine in Pilsen, Charles University in Prague, Czech Republic d Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University in Prague, Faculty Hospital Pilsen, Czech Republic e Department of Imaging Methods, Faculty of Medicine in Pilsen, Charles University in Prague, Faculty Hospital Pilsen, Czech Republic f Histology and Embryology, Department of Pathobiology, University of Veterinary Medicine Vienna, Austria E-mail address: [email protected] (K. Houdek) Introduction: A sterile inflammatory reaction that occurs in the aortic wall plays the main role in the etiopathogenesis of abdominal aortic aneurysm. Products containing statins may affect some processes involved in the systemic inflammatory response of the body and therefore they could decelerate growth of the aneurysms and prevent their rupturing. The authors want to present the results of their own study to document the effects of the statin preparations on growth of an experimentally created aneurysm in an animal. Method: We created an experimental aneurysm of the abdominal aorta in 27 pigs divided into two groups. Pigs in one group were treated by statins daily. The size of the aneurysms in all our probands was checked by ultrasound examination. After the measurement at the end of the fourth week we harvested the samples of the aneurysmatic
doi:10.1016/j.vph.2011.08.198
Objective: Abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AIOD) are common vascular disorders considered to be complex diseases with both genetic and environmental risk factors involved. Involvement of various matrix metalloproteinases is very important in the pathogenesis of these diseases. Matrix metalloproteinase-13 (MMP-13) was shown to be up-regulated in AAAs and atherosclerotic lesions of aorta. A functional MMP-13 promoter polymorphism (−77A NG) was found to be associated with functional status in rheumatoid arthritis. The aim of the present study was to examine if MMP-13 (−77A NG) gene polymorphism is a susceptibility factor of AAA or AIOD in Polish patients. Results: Based on a PCR-RFLP analysis the MMP-13 genotypes (A/ A; A/G/; G/G) were determined in three selected groups: 300 patients with AAA and 312 patients with AIOD who underwent surgery; 313 individuals from control group. Genotypes were compared with demographic and clinical data of subjects and analyzed in relation to risk factors. No significant differences in genotype distribution and allele frequencies of MMP-13 (−77A NG) gene polymorphism in the study groups were found. Conclusion: This study found no evidence of association of MMP13 (−77A NG) gene polymorphism with AAA or AIOD in Polish patients. doi:10.1016/j.vph.2011.08.199
379
the endothelium but also of a variety of chemokines which have chemotactic and proinflammatory properties thereby contributing to vascular remodeling and thus to increased stiffness. The aim of this study was to determine whether the inflammation markers hsCRP, CCL22/MDC and its regulatory cytokines IL-4 and IFNγ are associated with increased AoS measured by PWV. hsCRP, CCL22, IL-4 and IFNγ were determined by immunoassays in 87 patients 63.3 ± 49.7 months after surgery for type A aortic dissection. We tested for correlations between these and haemodynamic parameters including 24-hour SBP, carotid-to-femoral PWV and progression velocity of aortic dilation (vØ). We found PWV and 24-hour SBP to be significantly correlated (r = 0.39; p b 0.001; ß = 0.345; p = 0.002) indicating a strong link between increased SBP and AoS. Among the inflammation markers, only CCL22 was correlated to PWV (r = 0.309; p = 0.056). Using the recommended cut-off value of 12 m/s for PWV, CCL22 was significantly higher in the high (15.3 ± 2.6 m/s) than in the low (9.9 ± 1.5 m/s) PWV group (603 ± 173 vs. 455 ± 210 pg/ml; p = 0.020). Regarding vØ, we found a significant correlation with 24-hour SBP (r = 0.336; p = 0.026; ß = 0.324; p = 0.046) but not with PWV and with hsCRP (r = 0.412; p = 0.005; ß = 0.337; p = 0.038) but not with CCL22. Taken together, these data indicate that in this population, 1° uncontrolled hypertension is related to increased aortic stiffness, 2° CCL22 appears to be a sensitive and specific marker of aortic remodeling, 3° aortic dilation (vØ) is related to increased SBP but not to stiffness and 4° aortic dilation appears to be independent of the CCL22 cascade.
aorta. The acquired samples were further processed, fixated and investigated. The wall of the experimental aneurysm was described by means of various parameters. All selected parameters specifically describe the aortic wall both in terms of its structure and function (elastin and collagen fibres, different types of smooth muscle cells, beta-catenin, vascularization, width of layers of aortic wall). Study results: By comparing the size of the aneurysms we did not find any statistically significant differences between both groups. However, in the first group there was an apparent trend in growing of the aneurysms that we did not find in the second group of pigs treated with statins. In all listed evaluated parameters the animals treated with statins showed statistically significantly better parameters, which can be considered as a histological picture of the vascular wall which is more stable and less damaged. Discussion: Better preservation of the elastin net and the contractile phenotype of the smooth muscle cells in treated group is in accordance with the recently described anti-inflammatory effect of statins in experimental aneurysms that had an unambiguously protective effect directly preventing progression of the aneurysm (Shiraya et al., 2009). A favorable effect of statins may be associated with (non-lipid) mechanisms which modify the function of the endothel, smooth muscle cells and population of monocytes– macrophages in the vascular wall (Koh, 2000). Based on the acquired information we assume that therapy with statins could be beneficial in prophylaxis of fast growth and ruptures of small aneurysms.
doi:10.1016/j.vph.2011.08.197
P.14.3 MMP-13 (−77A NG) gene polymorphism is not a susceptibility factor of abdominal aortic aneurysm or aortoiliac occlusive disease Aleksandra Korcza, Oliwia Zakerskaa, Katarzyna Pawlaczykb, Marta Molinska-Glurab, Grzegorz Oszkinisb, Ryszard Slomskia, Marcin Gabrielb a Polish Academy of Sciences, Institute of Human Genetics, Poznan, Poland b Poznan University of Medical Sciences, Poznan, Poland E-mail address: [email protected] (A. Korcz)
P.14.2 Progression of experimental abdominal aortic aneurysm is mitigated by statins Karel Houdeka, Jiří Moláčeka, Vladislav Třeškaa, Věra Křížkováb, Lada Eberlováb,c, Lukáš Nedorostb, Jiří Kobrd, Jan Baxae, Kirsti Witterf, Zbyněk Tonarb a Department of Vascular Surgery, Faculty of Medicine in Pilsen, Charles University in Prague, University Hospital in Pilsen, Czech Republic b Department of Histology and Embryology, Faculty of Medicine in Pilsen, Charles University in Prague, Czech Republic c Department of Anatomy, Faculty of Medicine in Pilsen, Charles University in Prague, Czech Republic d Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University in Prague, Faculty Hospital Pilsen, Czech Republic e Department of Imaging Methods, Faculty of Medicine in Pilsen, Charles University in Prague, Faculty Hospital Pilsen, Czech Republic f Histology and Embryology, Department of Pathobiology, University of Veterinary Medicine Vienna, Austria E-mail address: [email protected] (K. Houdek) Introduction: A sterile inflammatory reaction that occurs in the aortic wall plays the main role in the etiopathogenesis of abdominal aortic aneurysm. Products containing statins may affect some processes involved in the systemic inflammatory response of the body and therefore they could decelerate growth of the aneurysms and prevent their rupturing. The authors want to present the results of their own study to document the effects of the statin preparations on growth of an experimentally created aneurysm in an animal. Method: We created an experimental aneurysm of the abdominal aorta in 27 pigs divided into two groups. Pigs in one group were treated by statins daily. The size of the aneurysms in all our probands was checked by ultrasound examination. After the measurement at the end of the fourth week we harvested the samples of the aneurysmatic
doi:10.1016/j.vph.2011.08.198
Objective: Abdominal aortic aneurysm (AAA) and aortoiliac occlusive disease (AIOD) are common vascular disorders considered to be complex diseases with both genetic and environmental risk factors involved. Involvement of various matrix metalloproteinases is very important in the pathogenesis of these diseases. Matrix metalloproteinase-13 (MMP-13) was shown to be up-regulated in AAAs and atherosclerotic lesions of aorta. A functional MMP-13 promoter polymorphism (−77A NG) was found to be associated with functional status in rheumatoid arthritis. The aim of the present study was to examine if MMP-13 (−77A NG) gene polymorphism is a susceptibility factor of AAA or AIOD in Polish patients. Results: Based on a PCR-RFLP analysis the MMP-13 genotypes (A/ A; A/G/; G/G) were determined in three selected groups: 300 patients with AAA and 312 patients with AIOD who underwent surgery; 313 individuals from control group. Genotypes were compared with demographic and clinical data of subjects and analyzed in relation to risk factors. No significant differences in genotype distribution and allele frequencies of MMP-13 (−77A NG) gene polymorphism in the study groups were found. Conclusion: This study found no evidence of association of MMP13 (−77A NG) gene polymorphism with AAA or AIOD in Polish patients. doi:10.1016/j.vph.2011.08.199